Clinical studies correlating active well differentiated thyroid carcinoma with circulating levels of human thyroglobulin (Htg) by radioimmunoassay suggest that the latter could conceivably replace other procedures e.g., total body scans as an effective method of patient evaluation. In a prospective cross sectional study, 90% of patients post thyroidectomy and post 131I ablation who have Htg levels less than 7 ng/ml, have negative total body scans, whereas, 100% of those patients with values greater than 7mg/ml, have positive scans showing evidence of residual tumor or normal thyroid tissue. The 10% of patients with positive scans and Htg levels less than 7ng/ml most likely have normal residual thyroid tissue since no evidence of metastases or residual tumor has been obtained. Chi square analysis of these data indicate that Htg levels accurately reflect total body thyroid scans (p less than .001). No longitudinal data using Htg have been reported and it is likely but unproven that Htg levels will be similarly effective. These data are important since they may provide an earlier diagnosis of tumor recurrence with associated earlier therapy. A longitudinal prospective study is proposed to assess the onset of metastases by total body scans compared to serum Htg levels. Total body thyroid scanning will be performed on a yearly basis for five years, whereas Htg levels will be determined with clinical examinations every six months for five years. These data should indicate whether Htg levels are more sensitive and/or specific than currently existing techniques and whether or not the Htg levels can replace this technique. Htg from tumor and normal thyroid tissue is immunologically identical; however, there are chemical and physical differences. Normal and tumor Htg will be purified and analyzed by a number of techniques. These forms of Htg will be assessed to evaluate circulating species of Htg that may be tumor markers. Thus, the goal of presurgical diagnosis of thyroid carcinoma is conceivable. The cost effective implications of preoperative diagnosis and improved longitudinal evaluation will have a major impact upon health care delivery in this country.